ativaÇÃo de linfÓcitos t
TRANSCRIPT
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ATIVAÇÃODELINFÓCITOST
• Histórico• AtivaçãodelinfócitosT:basesdaimunidade• ReconhecimentodeantígenosporTCR• ApresentaçãodeantígenosporAPC• RestriçãodeativaçãodelinfócitosT (controle)• Diferenciaçãodelinfócitos(T cell populations)• Sinapseimunológica• ControledaativaçãodeT
FMRP-USP,2019
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History of Vaccination: SmallpoxSmallpox killed or maimed 10% of humankind.
Killed > 300,000,000 people in the 20th century aloneAncient Chinese history: a once in a lifetime disease.
11th century China and India: “Variolation”Scratch a healthy person with pus from infected person
If they don’t die, they are immune for life
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May14,1796,EdwardJenner
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History of Vaccination• Despite Jenner’s success, it
took 100 years til the next vaccine.
• 1881, Louis Pasteur: coined the word Vaccine.– Used dried spinal cord from
rabid rabbit to create a rabies vaccine.
– Also developed vaccines to fowl cholera and anthrax
• July6,1885:9yearoldJosephMeisterwhowasbadlybittenbyarabiddog.
• AlthoughPasteurwasnotalicensedphysicianandfacedlegalrisks,theboywouldmostcertainlyhavediedwithouttreatmentlikemanybeforehim.
• PasteurdecidedtotreattheboyneverthelessandinoculatedJosephwithrabiesvaccinethathadbeentestedonlyondogspreviously.
• Theriskpaidoffandtheboyrecovereddramatically.
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Passive Immunity in Infants
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Artificial Passive Immunity
• Gamma globulin • Ig’s from pooled blood of at least 1,000 human
donors• variable content• non-specific
• Specific immune globulin (SIG)• higher titers of specific antibodies
• Antisera and antitoxins of animal origin
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Antibody and effector T-cells are the basis of protective immunity
•Primary infection stimulates an initial immune response.
•A second infection is “inapparant”because it provokes no symptoms.
•However, it does re-stimulate and fine tune the immune response.
•Years later, memory B- and T-cells can become reactivated upon infection, protecting the individual from disease
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Artificial Active Immunity
• Vaccination (Immunization)• exposing a person to material that is antigen but
NOT pathogenic.
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Componentes deuma vacina
Antígeno(Patógeno)
Formulação(Sistema deEntrega)
ProteínaCarboidratos
Especificidade
AdjuvantesVetores Virais
MagnitudeDuração
Tipo daresposta imune
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Whole agent vaccines -- Killed using heat or formaldehyde
Inactivated polio vaccine (Salk)
Influenza (Classic)
epitopes
epitopesLive virus Killed virus
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Whole agent vaccines --Attenuated• attenuated - a process that lessens the
virulence of a microbe
oral polio vaccine (Sabin),
MMR (measles, mumps, rubella)Influenza -- FlumistTM
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Vaccines stimulate immune memory
•Killed virus vaccine requires multiple doses (booster shots) to adequately stimulate a protective immune response
•Live virus vaccines replicate in the host.•No requirement for boosters.
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TCR & MHC/Pept
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COMPLEXO TCR
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FasesdasRespostasdeCélulasT
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DC:apresentaçãodeAgnosLNs
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Recirculação dosLinfócitos Tvirgens
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Fase1:ReconhecimentodoAntígenoCapturaeApresentação
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Entrada deLinfócitos Tvirgens em órgãosLinfóides
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Entrada deLinfócitos Tvirgens em órgãosLinfóides
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Células Apresentadoras deAntígenos
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MoléculasdeAdesão
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Fase 2:Ativação deLinfócitos
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Molécula Coestimuladora:CD28
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Fase 2:Ativação deLinfócitosPapel deMoléculas Coestimuladoras
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IL-2eIL2R
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Papel Biológico daIL-2Fase 3:Expansão Clonal
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Molécula Coestimuladora:CD40
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Sinal 3:CitocinasDiferenciação deLinfócitos T(Fase 4)
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AtivaçãodeLinfócitosT
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SinapseImunológica
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SinapseImunológica
NATUREREVIEWS|IMMUNOLOGY VOLUME3|DECEMBER2003
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SinalizaçãointracelularduranteativaçãodelinfócitosT
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Diferenciação deLinfócitos Th
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Diferenciação deTh1
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Diferenciação deTh2
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Diferenciação deTh17
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Papel deTh na diferenciação deTCD8
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www.nature.com/nri
O papel do linfócito T CD4+ helper na diferenciação de T CD8+
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MOLÉCULAS ACESSÓRIAS
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Co-estimulação e regulação negativa da ativação de linfócitos
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Estrutura do linfonodo e circulação de células
ww
w.nature.com
/reviews/im
munol.
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Interações moleculares na sinapse imunológica
www.nature.com/reviews/immunol.
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Modelo temporal de linfócitos T CD8+ durante uma infecção
www.nature.com/nri
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Células T CD8+ de memória
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FIM